Download Neonatal Mechanical Ventilation - Pediatric Emergency Medicine

Heliox as an Adjunctive Therapy to Treat
Rhinovirus/Enterovirus-Related
Respiratory Failure in Infants and
Children
Sherwin E. Morgan, RRT, RCP
Clinical Practice & Development / Educator/ Research
Coordinator
Department of Respiratory Care Services
Section of Pulmonary & Critical Care Medicine
The University of Chicago Medicine (UCM)
[email protected]
Conflict of Interest
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I have no real or perceived conflict of
interest that relates to this
presentation.
Any use of brand names is not in any
way meant to be an endorsement of
a specific product, but to merely
illustrate a point of emphasis.
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Respiratory syndromes caused by viral infections has been of
major global concern for the health care industry for centuries.
Significantly effect morbidity and mortality with regard to children
with and without premorbid conditions when associated with viral
bronchoconstriction related respiratory failure (RF).
Huge impact on global health care resources and finances
The etiology of respiratory infections, likely community acquired;
 easily spread & highly pathogenic
 replicate into different strains and/or structures
Possible root cause;
 epidemics
 pandemics
30 Years of Clinical Practice Observations
and Investigation - Lessons Learned
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Classification of Airflow Obstructions
• Airflow obstruction 1 - Asthma
• Airflow obstruction 2 – Viral Bronchiolitis
Clinical Identification of Respiratory Syndromes
• Clinical breathing-asthma scoring assessment (CBASA)
• Chest radiography
• Respiratory viral panel (RVP)
Respiratory Care Interventions for Airflow (AFO)
Obstruction;
• Volumetric aerosolized continuous Beta-agonist
• High Flow Nasal Cannula (HFNC)
• Mechanical Ventilation
• Helium- oxygen (Heliox) 80/20
Prevention and Vaccines
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Global influenza vaccine prevention.
 Most are developed for H-N influenza
 Vaccines are not available for viruses outside of H-N
influenza structure
Less effective against premorbid conditions and more acute
in situations such as;
• Exacerbation caused by cold and flu=respiratory distress
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Asthma - COPD
Immune compromised
Small infants and children
Malnourished
Pregnancy
Past 6W Chicago has experienced an increase of animal and UCM
25% increase of human flu ADMISSIONS.
Viral Respiratory Distress
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Same illness whether you are young or old
• common cold
• severe acute respiratory distress (SARS) - like
symptoms
Increasingly, respiratory syndromes such as Rhinovirus
and Enterovirus (RE) are recognized as precipitants of acute
respiratory distress and RF.
These illnesses mandate hospitalization.
Respiratory syndromes (RS) are grossly overlooked and
underestimated as the root cause of RF.
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It is important to accurately understand and identify the
source of respiratory distress, masquerades as asthma-like
Viral wheezing or bronchospasm – not simple asthma like
bronchospasm, actually related to fluid rhonchi / rales
related bronchoconstriction .
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Because initial differential diagnosis include asthma
• Leads to treatment confusion
• Too much focus on asthma component of AFO
• American Academy for Pediatrics' advise against use
of bronchodilator is controversial
First line beta-agonist medications are usually not effective
for relief of respiratory distress.
Influenza-Like Respiratory Syndromes
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Etiology of Viral related air gas flow obstruction;
 Airway wall (AWW) swelling-constriction - thickening
 AWW changes are not clearly defined. Hypothesis,
million of virus cells attack AWW and cause structure
change that is define as peri-bronchial wall thickening
 AWW structure changes temporary or permanent?
Infections are now documented to be caused by multiple
viral agents, starting to see patients with co-infections.
One pediatric patient back in PICU three times for viral
related RF (HCoV-229E & 2RE). Peri-bronchial airway
thickening on x-ray. Mechanical ventilation with heliox each
time.
Classification of Viruses, Known to be the Source of
Respiratory Syndromes that Effect Animals and
Humans
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Viruses linked to pulmonary exacerbations of; bronchitis,
bronchiolitis, and/or pneumonia in variable combinations, maybe
transmitted back and forth between humans and animals.
Caution: Do not underestimate these viruses, they can be deadly
Mainly classified as Influenza A and B (bird or swine) = H-N
• H1N1 -2009, California, Hong Kong, H2N2, H3N2, H5N1, H9N2
• Respiratory syncytial virus - (RSV)
• Coronavirus (HCoV), 229E, HRU, NL63, OC43
• Human Metapneumovirus
• Rhinovirus (HRV), HRV-A, HRV-B, HRV-C, HRV-D
• Enterovirus (EV). EV68, EV70, EV94
• Adenovirus
• Parainfluenza (1-4)
Clinical Bronchiolitis / Asthma
Scoring Assessment (CBASA)
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It is age specific
assessments that
includes;
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respiratory rate,
SpO2
dyspnea
chest retractions
Auscultations
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Results gives a
severity rating and
alert staff of when to
escalate care;
• Mild (5-7)
• Moderate (8-11)
• Severe (12-15)
Chest Radiography –
Interpretations of AFO
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Bronchiolitis
Peri-bronchial airway wall thickening
Retro-cardiac atelectasis, due to
mucus plugging
Reactive airways
Pneumonia
Dynamics of Air-flow Obstruction
related to Complex Respiratory Failure
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Type 1; AFO - Asthma
• Smooth muscle bronchospasm (lower airway)
• V/Q mismatch = Air-trapping in the lungs =
hyperinflation > hyper-oxygenation with
impaired ventilation, may impede MAP &
venous return.
Type 2; AFO – Bronchiolitis - Bronchoconstriction
• Etiology - viral, impedes alveolar gas exchange
at bronchial interstitium = hypercarbic
hypoxia = pulmonary arterial hypertension.
• If not recognized > ventilation + nitric oxide +
proning + Isoflurane = ECMO > tracheostomy
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Early detection and recognition of severity is critical for
survival if detected before co-morbidities set in such as;
ARDS, kidney failure and organ failure.
Move the patient earlier rather than later for rescue
therapies to be effective.
ECMO mortality rate is 38% = more complications
Heliox use as an adjunctive treatment is not well studied for
hypercarbic RF of unknown origin, should be used early.
Bell curve – assessment
Once there are infiltrates on x-ray = ARDS.
Kidney failure – prognosis is poor
The ship is in port and ready to sail
Heliox
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Helium – oxygen (heliox), has been used for
more than a century to treat obstructive
pulmonary disease.
Specialty gas 80% helium-20% oxygen.
The lower density and higher viscosity of
heliox gas mixtures relative to nitrogen-oxygen
can significantly reduce airway resistance (RAW)
Clinical Indications for Heliox
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Clinically, heliox can decrease RAW when associated with;
• Asthma
• COPD
• upper airway obstructions
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Croup
Post extubation stridor
Subglottic edema
Heliox may enhance the bronchodilating effect of B-agonist
Products now being produced world wide to interface with
today’s respiratory care bedside equipment. (mechanical
ventilator - Hamilton G5 & Servo-1; heliox blenders, by
Precision Medical® and VapoTherm®).
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I present the case review of three patients who
presented with influenza-like respiratory
syndrome RF who were treated with adjunctive
heliox. Who experienced resolution of their
respiratory failure through the use of heliox.
 Rhinovirus/Enterovirus.
 One had co-infection HCoV-43
Case Review
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A 10 month-old Hispanic male with a history of
seizures was intubated in the field during a
seizure episode.
He was transported to Comer Children’s Hospital
at The University of Chicago Medicine (UCM)
He was admitted to PICU for ventilator
management and started on anti-seizure
medications
Morgan et al Respir Care 2014
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Chest radiograph =
• left lower lobe opacity; atelectasis or
pneumonia
The RVP was positive: Polymerase chain reaction
(PMR).
• Rhinovirus / Enterovirus.
• HCoV- 43
• Air borne droplet and contact pre-cautions
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Over the next 2d seizures were controlled
He was extubated and placed on High
Flow Nasal Cannula (HFNC) (Fisher &
Paykel RT329), FIO2-1.0 at 5 L/min,
breathing at >50 breaths/min.
Q2 h beta agonist nebulizer treatment and
chest physiotherapy
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He had no wheezing or stridor,
• coarse diminished breath sounds.
• intermittent fevers,
• suprasternal chest retraction graded as +5
using the pediatric advanced life support scale
Agitated and fighting face mask treatments
changed to Aerogen Solo® nebulizer via HFNC, all
aerosolized medication given with this method
there after.
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Despite the intense respiratory care
treatment regime, reminded in acute
respiratory distress.
• Respiratory rates - 60 to 70
breaths/min,
• continued prominent chest wall
retractions
• 24 hours post-extubation
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In addition, he experienced periods
of arterial desaturation down to 80%
that was measured by pulse
oximetry (SpO2).
• ? Chemoreceptor response
• Continue Inhaled beta-agonist
• Administered intravenous
corticosteroids
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The pediatric ICU team became concerned
that he was depleting his respiratory
muscle reserve due to increased work of
breathing (WOB)
AFO was thought to be post extubation
related distress originally.
• desaturation despite HFNC targeting an
FIO2 of 1.0.
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More aggressive respiratory options were
considered;
• Bi-level
• Infant nasal CPAP
• re-intubation.
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patients with air-flow obstruction can be
very complex to manage on positive
pressure ventilation. Therefore, a trial of
heliox via HFNC was attempted to reduce
RAW and possibly prevent re-intubation,,
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The American Academy for Pediatrics (AAP) definition of
severe acute respiratory distress in infant and children is
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Respiratory rates; 60 to 70 breaths/min
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Pre heliox treatment; respiratory rate assessment –
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60 to 70 breaths/min
• prominent chest retractions,
• nasal flaring
• suprasternal chest retractions
Heliox and HFNC Set-up
Heliox Blender
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HFNC @ 5 L/min, SpO2 was 94%
SpO2 would intermittently drop down to as low as
84% before heliox.
HFNC /Heliox flow calculations, heliox flow
started at 8 L/min with oxygen flow at 1 L/min =
total flow of 9 L/min
He was started 70% helium and 30% oxygen,
then changed to 60/40
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One minute after heliox initiation;
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Resp. rate fell to 31 to 36 breaths/min.
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chest retractions & nasal flaring improved
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Appeared to be in less distress, not
working as hard to breath.
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during the first 24h of heliox
• respiratory rate increased to 50 to 60
breaths/min,
• retraction returned
• SpO2 fell to 89%
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Upon investigation, heliox gas line had
become disconnected from the HFNC.
heliox gas line was reconnected,
• respiratory rate decreased to 27 breaths/min
• SpO2 improved to 96%.
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After heliox initiation, the patient’s
condition improved from critical to
serious/stable.
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Bronchiolitis, aerosolized Pulmicort (0.25 mg)
 every 12h with heliox augmented HFNC
 Racemic epinephrine tx via heliox-HFNC
There was no respiratory deterioration.
With improvement in his respiratory status,
 albuterol treatment decreased to every 4h
as needed.
 Nutritional support
 CPT continued
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heliox was discontinued on day 3
HFNC oxygen flow was 7 L/min and
Pulmicort remained at every 12h.
discharged from PICU to a floor on
day 10.
7 d later, discharged home with clinic
follow-up
Ventilator & Heliox Management Strategies:
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Set tidal Volume at 4-5 cc/kg
Control mode and age specific set breaths/min (deep
sedation & paralytics)
Ventilate using plateau pressure (Pplateau) as lung
pressure measurement
• Pplateau < 30 cm H2O, look for auto-PEEP
Set helium to oxygen concentrations to an FIO2 to achieve
or maintain SpO2 > 88%
Permissive hypercapnia to avoid ventilator associated lung
injury (VALI)
pH / PCO2 – Historical Control
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Patient
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
pH-t=1 pH-t=2
7.30
7.36
7.27
7.28
7.33
7.36
7.28
7.54
7.13
7.13
7.30
7.30
7.03
7.05
6.98
7.05
7.09
7.29
7.07
7.10
7.14
7.14
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P=.04
Mean
7.16
7.24
SD
0.12
0.16
Shaffer et al Critical Care Med 1999
PaCO2- t=1
36
46
36
64
64
46
60
125
82
65
74
63
25
PaCO2-t=2
29
46
30
31
70
39
85
102
54
62
70
P=0.17
56
24
Alveolar-arterial Oxygenation
Gradient - Control
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Patient
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
Mean
SD
A-a t=1 A-a t=2
177
104
185
216
221
124
273
213
227
224
183
208
207
270
345
226
395
171
153
120
126
117
P=0.09
226
181
82
56
FIO2 t=1
1.0
.60
1.0
.60
.60
--.60
.60
1.0
.60
1.0
.80
21
FIO2 t=2
.50
.60
.60
.60
.60
--.60
1.0
.06
.40
.60
P=0.07
.62
15
pH / PCO2 - Heliox
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Patient
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
Mean
SD
pH-t=1 pH-t=2
7.12
7.17
7.17
7.15
7.33
7.31
7.28
7.28
7.07
7.05
6.79
7.07
7.12
7.08
7.33
7.33
6.87
7.00
7.00
7.16
7.22
7.31
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P=.09
7.12
7.17
0.18
0.12
PaCO2- t=1
83
63
42
69
85
197
66
46
137
128
66
89
47
PaCO2-t=2
71
61
49
71
61
102
86
46
91
89
56
P=.06
70
21
Alveolar-arterial Oxygenation
Gradient - Heliox
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Patient
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
Mean
SD
A-a t=1 A-a t=2
332
70
147
54
181
85
405
55
217
181
255
144
231
78
146
226
216
84
179
104
68
36
P=0.001
216
85
92
44
FIO2 t=1
.70
1.0
1.0
.80
1.0
1.0
1.0
.60
1.0
.40
.40
.81
.25
FIO2 t=2
.30
.30
.25
.30
.50
.50
.30
1.0
.60
.40
.40
P=0.002
.37
.12
MAQUET® Servo-I Heliox
Volumetric Medication Delivery
Case study #2
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4 year old white female 16.5 kg was
transferred to Comer’s Children’s
Hospital at UCM due to hypercarbic
RF (PaCO2-118 mmHg)
no previous documentation for a
history of asthma
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Intubated at OSH
Difficult to ventilate with ventilator and transport
team had to hand ventilate for transport
Chest Radiography –
• moderate peri-bronchial thickening
RVP indicated:
• Rhinovirus-Enterovirus (RE).
Medication list for 24h before heliox
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Continuous albuterol nebulizer
Aminophylline
Cisatracurum
Fentanyl
Ketamine
Midazolam
Terbutaline
MethylPREDISolone
Atrovent
Budnesonide
15 mg/hr
1 mg/kg/hr
0.1 mg/kg/hr
1.5 mcg/kg/hr
20 mcg/kg/hr
0.07 mg/kg/hr
2.5 mcg/kg/hr
1 mg/kg – Q6
500 mcg – Q2
0.5 – Q12
ABG Before Heliox = T1 - T2=3h Later
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T1
PH
6.99
PaCO2
107
PO2
73
FIO2/helium .60
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Vent setting; VT 140, PRVC -18, FIO2/heliox - 60/40, +5 PEEP.
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T2
7.11
77
97
60/40
Day 2
7.37
60
77
50/50
PAW – 36 cm H2O, plateau pressure-22cm H2O, Set PEEP +5 cm
H2O, total PEEP +9 cm H2O, air-trapping not observed.
Heliox D/C after two days, stayed on the ventilator for 8 days.
Her course was complicated by severe post sedation delirium.
Case study #3
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36 year old male African American with a history
of asthma.
Transferred to UCM for management of
hypercarbic RF.
Air transported to UCM for evaluation for possible
ECMO for asthma:
Initial management:
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intravenous corticosteroids – MethylPREDNISLONE - 40 mg,
continuous beta agonist – 15 mg/hr x 72 hr
non-invasive mask ventilation
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Respiratory acidosis (PaCO2-115 mmHg)
progressed
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Isoflurane was administered:
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required mechanical ventilation (MV),
deep sedation -(Propofol 1% and Fentanyl 1000mcg
Paralytic – (Cisatracurium = 1 - 5mcg/kg/min
relieve bronchospasm
improve alveolar ventilation.
Upon arrival at UCM MICU PaCO2 – 111
mmHg
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He was placed on a heliox compatible
ventilator in the assist control mode.
Chest radiography was notable;
• retro-cardiac atelectasis, likely due to
mucus plugging.
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RVP, abnormal positive for Rhinovirus /
Enterovirus.
ABG Before Heliox = T1 - T2=3h Later
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pH
PaCO2
PaO2
PAW
Pplat
11:45a
7.19
111
48
55
39
15:30p
7.38
71
54
54
22
Day 2
7.52
54
60
60
21
Vent setting; VT - 450, assist control -10 - 12, HO/FIO2 ratio – 70/30, set
PEEP +5.
He was given a spontaneous breathing trial and extubated three days after
transfer. Follow-up chest radiography demonstrated peri-bronchial wall
structure thickening
His course was complicated by significant weakness, likely due to
prolonged neuromuscular blockage
Discussion
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Respiratory syndromes are frequent trigger for status
asthmaticus like exacerbations, that are difficult to manage
even with today modern day medicine.
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Viral related bronchoconstriction appears to be the etiology
of influenza like RF .
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Heliox has been used for over a century to treat pulmonary
exacerbations,
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though little data evidence exist regarding the efficacy of
heliox for the treatment of viral related pulmonary
exacerbations.
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The use of heliox was first reported in 1935 by
Alvin Barach.
He observed that breathing heliox appeared to
relieve dyspnea in children and adults with
asthma and upper airway obstruction.
In 1950, Barach, Peabody and Levine, called it
generalized obstruction or partial obstruction of
the airway, general appearance of asphyxiation
accompanied with rapid shallow breathing. “Total
obstruction not compatible with the living”.
• Although the earlier reports were noncontrolled, the improvement observed in
these patients strongly suggest an
positive effect of breathing heliox on
RAW.
• In addition, as witnessed in our case,
• Relapse occurred when heliox was
discontinued even briefly.
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Regardless of the possible
contributions, our patient’s appeared
to respond to inhaled helium oxygen
mixtures.
The morbidity and mortality is
significant with regard to infants
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Viral respiratory AFO is like flying an
airplane, with turbulent air flow.
You have to trust clinical instruments
and clinical information.
Chest radiography, CBASA, and RVP
Application of heliox is not widely
recognized and considered an
adjunct
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Between 2012 and 2014, over 1,200 kids were
admitted for one or another respiratory
syndromes, some patients had co-morbiditites
In the summer of 2014 > 600 kids were admitted
to Comer Children’s Hospital, 12 cases were near
fatal, 2 went on ECMO, one fatal.
Many kids treated with heliox combinations
Bilevel, HFNC and MV.
The majority of the kids were diagnosed with the
Rhinovirus / Enterovirus
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Few prospective studies have
examined the use of heliox for
respiratory syndromes.
Martinon-Torres et al, investigated
38 non-intubated infants with RSV
Using a modified version of the
Wood’s CASA.
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They found significant improvement
in scores with heliox after 1h of
treatment compared with the control
group.
The total average decrease in scoring
was;
• 4.2 in the heliox group versus
• 2.5 in the control group
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Kim et al, performed a randomized control trial
with 69 spontaneously breathing infants
diagnosed with RSV related viral bronchiolitis
Found a mean change from baseline of;
• 1.84 CASA for the 70/30 heliox group
• 0.31 for the oxygen group.
The only prospective study for the use of heliox
for acute viral bronchiolitis in spontaneous
breathing children was performed by Hollman et
al, 1996.
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The beneficial effects of breathing heliox is
derived
• from reduction in air-flow resistance
• restoration of laminar gas flow to airways
• that are obstructed from per-bronchial
thickening or mucus plugging
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In normal human airways, the resistive
pressure decrease between the glottis and
tenth-generation airways varies directly
with inspired gas density
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The resistive pressure decrease over
the tenth to twentieth generation is
density-independent because air-flow
in these regions is laminar.
Because 80% of the inspiratory
resistive pressure decrease occur in
the more proximal densitydependent segments,
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Breathing a less dense gas can reduce RAW
to 28 - 49% of that measured with air in
normal patients.
RAW;
• Normally < 3 cm H2O/L/s,
• 40% pressure reduction is clinically
unimportant.
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However, in asthma and other causes of
influenza-like viral airflow obstruction
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RAW can increase to > 50 cm H2O/L/s with much
of this related to air-flow obstruction from
turbulent gas flow associated with airway
constriction from;
• peri-bronchial airway wall structure thickening
• atelectasis related mucus plugging
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Studies indicate that bronchiolitis is a
heterogeneous disease and involves smaller
airway and lung interstitium
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Often overlooked, It appears as if
bronchoconstriction may be the
etiology behind influenza-like
respiratory failure.
Maybe the main source of obstruct
air flow and medication entry the
lung for gas exchange to occur.
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Because heliox reduces non-laminar air
flow, diverse causes of airway disease
leading to air-flow obstruction are likely to
respond to heliox administration.
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The use of heliox in this situation does not
treat the underlying disease or influence
the anatomy of the airway.
Rather, heliox is used as a bridge
treatment
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•
•
•
•
to reduce airflow resistance,
until definitive therapies and
time act to reduce RAW
reduce the need for heliox,
usually within 24 to 48 h.
Conclusion
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More than a century has passed,
• there are inadequate studies to
definitively determine the role of heliox,
and its appropriate place in the
armamentarium against respiratory
syndromes exacerbations.
• Which has now shown the ability to
effect large populations of animals and
humans
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To our knowledge, few reports exist with
regard to the use of heliox being
administered as an adjunctive treatment
for viral influenza-like respiratory failure
with resolve.
The hypothesis was that the combination
of treatments may have had a cumulative
therapeutic effect for the attenuation of
acute air-flow obstruction


Clinically, these patient’s breathing
improved with heliox treatment
All three patient’s general condition
continued to improve after 48 h of
• heliox
• aerosolized corticosteroids
• nutritional support

The benefit of heliox itself appeared
to serve as a bridge to support these
patients while time and
pharmacologic measures took effect
and an underlying infection abated.


Because patient response may vary,
a trial of heliox should be considered
when caregivers are confronted with
patients with acute air-flow
obstruction who still have respiratory
reserve and refractory to current
treatment methods.
The patient should be monitored
closely for acute changes.


More prospective study are needed to
understand, recognize and treat viral
related airflow obstruction and the role of
heliox for the treatment of viral pulmonary
exacerbation
which is now documented to be caused by
an increased number of viral agents.
References
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